Oculopharyngodistal myopathy （OPDM） is a hereditary neuromuscular disorder occurring in adolescence or early adulthood and is characterized by slowly progressive external ophthalmoplegia， facial muscle weakness， dysphagia， and distal limb weakness. This article reports a patient with OPDM type 4 who had the initial presentation of bilateral pyroptosis and external ophthalmoplegia and was misdiagnosed with thyrotoxic myopathy， and later the patient developed the clinical manifestations of bilateral masticatory and facial muscle weakness， bulbar paralysis， and limb weakness. Genetic testing revealed abnormal CGG repeat expansion in the RILPL1 gene. The clinical data of the patient was analyzed， and a literature review was performed， so as to improve the awareness of this condition among clinicians.

Background Lead smelting workers are exposed to mixed heavy metals such as lead (Pb) and cadmium (Cd). However, the specific associations and molecular mechanisms by which their combined exposure induces genetic damage remain unclear. Objective To clarify the association between combined Pb-Cd exposure and genetic damage and to explore the possible biological mechanisms through occupational epidemiological investigations and animal experiments. Methods (1) Population study: A cross-sectional study was conducted on 374 lead smelting workers in northern China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary levels of 8 metals including Pb and Cd, and graphite furnace atomic absorption spectroscopy (GFAAS) was used to quantify blood levels of Pb and Cd. The cytokinesis-block micronucleus assay (CBMN) was used to assess genetic damage. Poisson regression was used to analyze the association between metal exposure and micronucleus rates. (2) In vivo experiment: Thirty SD rats were randomly assigned to five groups: control (pure water), Pb (300 mg·L⁻¹ lead acetate), Cd (50 mg·L⁻¹ cadmium chloride), combined exposure (Pb + Cd), and resveratrol intervention (Pb + Cd + 50 mg·L⁻¹ resveratrol). After 8 weeks of ad libitum drinking water exposure, liver pathology, oxidative stress indicators [reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)], genetic damage (Comet assay and γ-H2AX) were evaluated. Furthermore, cell cycle distribution, apoptosis rates, and mRNA expression of DNA damage response (DDR), DNA repair, and apoptosis-related genes were measured. Results (1) The geometric mean (GM, 95%CI) of urinary Pb and Cd were 14.69 (13.14, 16.51) µg·L⁻¹ and 2.11 (1.90, 2.33) µg·L⁻¹, respectively; the blood Pb and Cd levels were 117.10 (105.59, 129.87) µg·L⁻¹ and 4.55 (4.23, 4.89) µg·L⁻¹, respectively among the 374 workers. The mean micronucleus rate was (1.64±0.081) ‰, with significantly higher rates in males (1.65±0.083) ‰ than females (1.53±0.334) ‰ (U=4.166, P=0.041). All Pb and Cd biomarkers were positively correlated with micronucleus rate (FR>1, P<0.05), with a significant interaction effect observed between Pb and Cd (FR>1, P<0.05). (2) In rats, co-exposure to Pb and Cd caused liver tissue damage and inflammatory infiltration. Significant increases were observed in lymphocyte ROS; GSSG and MDA in lung tissue increased, while GSH and CAT activity decreased. Comet assay indicators and γ-H2AX levels were significantly elevated. Co-exposure induced S-phase arrest and increased apoptosis. mRNA levels of DDR (ATM, ATR, Chk2, and P53) and pro-apoptotic genes (Bax and Caspase-3) were upregulated, while the anti-apoptotic gene Bcl-2 and DNA repair genes (BRCA1, BRCA2, RAD51, RAD52, and CtIP) were downregulated. Two-way ANOVA confirmed synergistic effects on GSSG, Comet assay indicators, and ATR/Chk2 mRNA expression. Conclusion Occupational co-exposure to Pb and Cd synergistically induces genetic damage. This damage is mediated by oxidative stress and DNA damage, which activates the DDR pathway and inhibits the expression of DNA repair genes, ultimately leading to cell cycle arrest and apoptosis.

Background Lead smelting workers are exposed to mixed heavy metals such as lead (Pb) and cadmium (Cd). However, the specific associations and molecular mechanisms by which their combined exposure induces genetic damage remain unclear. Objective To clarify the association between combined Pb-Cd exposure and genetic damage and to explore the possible biological mechanisms through occupational epidemiological investigations and animal experiments. Methods (1) Population study: A cross-sectional study was conducted on 374 lead smelting workers in northern China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary levels of 8 metals including Pb and Cd, and graphite furnace atomic absorption spectroscopy (GFAAS) was used to quantify blood levels of Pb and Cd. The cytokinesis-block micronucleus assay (CBMN) was used to assess genetic damage. Poisson regression was used to analyze the association between metal exposure and micronucleus rates. (2) In vivo experiment: Thirty SD rats were randomly assigned to five groups: control (pure water), Pb (300 mg·L⁻¹ lead acetate), Cd (50 mg·L⁻¹ cadmium chloride), combined exposure (Pb + Cd), and resveratrol intervention (Pb + Cd + 50 mg·L⁻¹ resveratrol). After 8 weeks of ad libitum drinking water exposure, liver pathology, oxidative stress indicators [reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)], genetic damage (Comet assay and γ-H2AX) were evaluated. Furthermore, cell cycle distribution, apoptosis rates, and mRNA expression of DNA damage response (DDR), DNA repair, and apoptosis-related genes were measured. Results (1) The geometric mean (GM, 95%CI) of urinary Pb and Cd were 14.69 (13.14, 16.51) µg·L⁻¹ and 2.11 (1.90, 2.33) µg·L⁻¹, respectively; the blood Pb and Cd levels were 117.10 (105.59, 129.87) µg·L⁻¹ and 4.55 (4.23, 4.89) µg·L⁻¹, respectively among the 374 workers. The mean micronucleus rate was (1.64±0.081) ‰, with significantly higher rates in males (1.65±0.083) ‰ than females (1.53±0.334) ‰ (U=4.166, P=0.041). All Pb and Cd biomarkers were positively correlated with micronucleus rate (FR>1, P<0.05), with a significant interaction effect observed between Pb and Cd (FR>1, P<0.05). (2) In rats, co-exposure to Pb and Cd caused liver tissue damage and inflammatory infiltration. Significant increases were observed in lymphocyte ROS; GSSG and MDA in lung tissue increased, while GSH and CAT activity decreased. Comet assay indicators and γ-H2AX levels were significantly elevated. Co-exposure induced S-phase arrest and increased apoptosis. mRNA levels of DDR (ATM, ATR, Chk2, and P53) and pro-apoptotic genes (Bax and Caspase-3) were upregulated, while the anti-apoptotic gene Bcl-2 and DNA repair genes (BRCA1, BRCA2, RAD51, RAD52, and CtIP) were downregulated. Two-way ANOVA confirmed synergistic effects on GSSG, Comet assay indicators, and ATR/Chk2 mRNA expression. Conclusion Occupational co-exposure to Pb and Cd synergistically induces genetic damage. This damage is mediated by oxidative stress and DNA damage, which activates the DDR pathway and inhibits the expression of DNA repair genes, ultimately leading to cell cycle arrest and apoptosis.

Objective To analyze the spatiotemporal distribution characteristics of and trends in the disease burden of dengue fever in China from 2005 to 2024, so as to provide insights into formulation of dengue fever control strategies. Methods Data pertaining to dengue fever cases in China from 2005 to 2024 were retrieved from the Infectious Disease Reporting Information System of Chinese Center for Disease Control and Prevention, and city population, gross domestic product (GDP), GDP per capita, and consumer price index in China were captured from the China Statistical Yearbook, National Bureau of Statistics of China, the China City Statistical Yearbook, and bureaus of statistics in each city. The disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) due to dengue fever were calculated in China from 2005 to 2024. The direct and indirect economic burdens of dengue fever were estimated to calculate the total economic burden. The trends in the disease burden of dengue fever were estimated in China from 2005 to 2024 using a Joinpoint regression model with the software Joinpoint 4.9.0.0, and the average annual percent change (AAPC) and its 95% confidence interval (CI) were calculated. In addition, the DALYs rate and economic burden of dengue fever in China were subjected to global and local spatial autocorrelation analyses using the software ArcGIS 10.8. Results The gross DALYs due to dengue fever were 5 558 person-years in China from 2005 to 2024, and the DALYs of dengue fever increased from 36 person-years in 2005 to 899 person-years in 2024, with an increase of 23.97 folds. The average annual DALYs rate of dengue fever was 0.02 person-years/10⁵ in China during the 20-year study period from 2005 to 2024, and the DALYs rate peaked in 2014 (0.13 person-years/10⁵) and reduced during the COVID-19 pandemic from 2020 to 2022. YLDs were the main contributor of DALYs due to dengue fever in China from 2005 to 2024, with a total of 5 354 person-years, accounting for 96.33% (5 354 person-years/5 558 person-years) of the gross DALYs. The gross DALYs of dengue fever were 2 982 person-years among men (53.66%) and 2 575 person-years among women (46.34%) in China from 2005 to 2024, and high DALYs of dengue fever were measured among residents at ages of 15 to 30 years (1 639 person-years), 30 to 45 years (1 857 person-years), and 45 to 60 years (1 204 person-years), respectively, accounting for 84.56% (4 700 person-years/5 558 person-years) of total DALYs due to dengue fever in China. The total economic burden of dengue fever was estimated to be 612 million Yuan in China from 2005 to 2024, with an average annual economic burden of 30.584 million Yuan. The economic burden of dengue fever increased from 196 000 Yuan in 2005 to 121 million Yuan in 2024 in China, with an increase of 616.35 folds, and the per capita economic burden increased from 3 322.21 Yuan in 2005 to 4 940.01 Yuan in 2024, with an increase of 48.70%. Dengue fever cases were reported in 274 cities (counties) across 31 provinces (autonomous regions, municipalities) in China from 2005 to 2024, with relatively higher DALYs in Guangdong Province and Yunnan Province. Spatial autocorrelation analysis revealed that the disease burden of dengue fever appeared positive aggregation in Chinese cities (counties) from 2005 to 2024 (global Moran’s I = 0.045, Z = 2.24, P < 0.05), with high-high clusters mainly concentrated in the Pearl River Delta region in Guangdong Province and Xishuangbanna Dai Autonomous Prefecture and Pu’er City in Yunnan Province, and the total economic burden (global Moran’s I = 0.032, Z = 9.55, P < 0.001), per capita economic burden (global Moran’s I = 0.208, Z = 27.34, P < 0.001), and the proportion of total economic burdens in GDP in 2024 (global Moran’s I = 0.017, Z = 5.91, P < 0.001) all presented positive aggregation, with relatively higher total economic burdens mainly concentrated in Guangdong Province and Yunnan Province. Joinpoint regression analysis showed that the gross DALYs rates of dengue fever appeared an overall tendency towards a rise in China from 2005 to 2024 (AAPC = 16.24%, P = 0.029), and the DALYs rate presented an overall tendency towards a rise among both men (AAPC = 14.75%, P = 0.028) and women (AAPC = 14.93%, P = 0.037) during the study period. The per capita direct economic burden appeared an overall tendency towards a rise among dengue fever patients in China from 2005 to 2024 (AAPC = 2.16%, P = 0.012); however, there was no significant difference in the trends in the per capita indirect economic burden (AAPC = 0.46%, P = 0.470). In addition, the DALYs rate of dengue fever appeared a tendency towards a rise in 84.67% (232/274) of cities (counties) in China from 2005 to 2024, and the per capita economic burden appeared a tendency towards a rise in 85.40% (234/274) of cities (counties), while the DALYs rate and per capita economic burden of dengue fever appeared a tendency towards a rise in 77.01% (211/274) of cities (counties). Conclusions The disease burden of dengue fever significantly increased in China from 2005 to 2024. It is recommended to reinforce integrated dengue fever control in high-risk areas and among high-risk populations, and to improve the surveillance of imported dengue fever cases and vector control.

ObjectiveTo investigate the potential mechanism of Huatan Sanjie Formula （化痰散结方， HSF） in the treatment of triple negative breast cancer （TNBC） based on the integrinβ1/focal adhesion kinase/yes-associated protein （integrinβ1/FAK/YAP） mechanotransduction signaling pathway. MethodsFifty BALB/c mice were randomly assigned to a model group， doxorubicin group， low-， medium-， and high-dose HSF groups， with 10 mice per group. An orthotopic TNBC transplantation model was established in all mice using syngeneic implantation of 4T1 cells. After successful modeling， mice in the model group received intragastric administration of normal saline 0.2 ml each day. Mice in the low-， medium-， and high-dose HSF groups received HSF by gavage at doses of 5.99， 11.97， and 23.94 g/（kg·d）， respectively. The doxorubicin group received intraperitoneal injections of doxorubicin （1.5 mg/kg） once every two days. All treatments lasted for 30 days. After the final administration， mice were sacrificed， and tumor weight and volume were measured. Hematoxylin-eosin （HE）， Masson's trichrome， and Sirius Red staining were performed to evaluate histopathological changes and collagen fiber deposition in tumor tissues. TUNEL staining was used to assess apoptosis. The Young's modulus of tumor tissues was measured using atomic force microscopy （AFM）. The nuclear-cytoplasmic localization of YAP was determined by immunofluorescence staining. Protein expression levels of integrinβ1， focal adhesion kinase （FAK）， YAP， and phosphorylated focal adhesion kinase （p-FAK） were detected by Western Blotting. The mRNA expression levels of integrinβ1， FAK， and YAP were assessed by quantitative real-time polymerase chain reaction （qRT-PCR）. Pearson correlation analysis was performed to evaluate the relationships among tumor tissue Young's modulus， apoptosis rate， and the expression levels of proteins related to the integrinβ1/FAK/YAP signaling pathway. ResultsCompared to the model group， tumor weight was significantly reduced in the doxorubicin group and the medium- and high-dose HSF groups， while tumor volume significantly decreased in the doxorubicin group and the high-dose HSF group （P＜0.01）. Tumor weight in the high-dose HSF group was significantly lower than that in the low-dose group， and tumor volume was significantly smaller than that in both the low- and medium-dose groups （P＜0.05）. Marked improvements in histopathological morphology were observed in the medium- and high-dose HSF groups and the doxorubicin group， while the proportion of collagen fiber deposition and the nuclear-to-cytoplasmic ratio of YAP were significantly reduced （P＜0.01）. Compared to the model group， all three HSF groups and the doxorubicin group exhibited significantly increased apoptosis rates， decreased Young's modulus， and reduced mRNA expression levels of integrinβ1， and YAP （P＜0.05 or P＜0.01）. Furthermore， protein expression levels of integrinβ1， p-FAK， and YAP in the high-dose HSF group were significantly lower than those in the model group （P＜0.05 or P＜0.01）. Pearson correlation analysis demonstrated a significant negative correlation between tumor tissue Young's modulus and apoptosis rate （r =-0.93， P＜0.01）. In contrast， the protein expression levels of integrinβ1， p-FAK， and YAP were positively correlated with Young's modulus （r=0.88， 0.97， and 0.98， respectively； P＜0.05） and negatively correlated with apoptosis rate （r=-0.93，-0.97， and -0.93， respectively； P＜0.05）. ConclusionHSF can significantly inhibit tumor growth in TNBC model mice. Its antitumor effect may be associated with reducing tumor tissue stiffness through suppression of the integrinβ1/FAK/YAP mechanotransduction signaling pathway.

Objective To analyze the diagnosis, treatment and clinical characteristics of a patient with parotid gland metastasis of clear cell renal cell carcinoma(ccRCC)following radical nephrectomy. Methods The clinical data and diagnostic/therapeutic course of the patient were reported, and the metastasis time and treatment methods of patients with parotid metastasis of renal cancer were summarized in combination with literature. Results The 63-year-old male patient sought medical help due to a mass behind the right ear persisting for 3 months. He had undergone a right radical nephrectomy for a renal tumor 10 years ago. Preoperative computed tomography(CT)with contrast of the parotid region revealed an approximately 2.5 cm×2.1 cm round soft-tissue density lesion in the right parotid gland with slightly irregular margins. Positron emission tomography/computed tomography(PET/CT)showed an enlarged left kidney with an irregular shape and multiple round, slightly hyperdense lesion(SUVmax=7.2), suggestive of malignancy. A round, slightly hyperdense lesion(diameter 2.6 cm, SUVmax=4.2)with well-defined borders and increased radiotracer uptake was noted in the right parotid gland, indicating a hypermetabolic mass where malignancy could not be excluded. The patient subsequently underwent partial parotidectomy, advancement flap transplantation, and facial nerve dissection. Postoperative pathology revealed tumor cells with clear/eosinophilic cytoplasm and nuclear atypia, exhibiting ill-defined borders with salivary gland tissue. Immunohistochemistry was positive for PAX-8, CAⅨ, and Ki-67. During the 12-month follow-up, the patient was in good condition with no evidence of tumor recurrence or metastasis. Conclusion Parotid gland metastasis following radical nephrectomy is exceedingly rare, with no specific imaging features and clinical manifestations, and definitive diagnosis relies on pathological examination. Currently, there is no standardized treatment protocol, but complete surgical excision remains the primary therapeutic option.

Objective To analyze the risk factors of plastic bronchitis (PB) in children with severe mycoplasma pneumoniae pneumonia (SMPP) and construct a Nomogram model. Methods A total of 195 children with SMPP from April 2022 to April 2025 were selected and divided into the PB group and the non-PB group according to the occurrence of PB. Their clinical data were compared. Binary logistic regression was used to analyze the risk factors of PB in SMPP, and ROC was used to analyze the predictive ability of the model. The Nomogram prediction model was established using R-4.4.3 software, and the calibration curve and clinical decision curve were plotted for analysis. Results PB occurred in 66 cases (33.85%) (P < 0.05). The duration of fever, PIV, SII, D-D, LDH, and pleural effusion were independent risk factors for PB in SMPP (OR=6.997, 1.016, 1.008, 70.202, 1.025, 32.323, P < 0.05). Based on this, the PB prediction model for SMPP occurrence established had a good goodness of fit (P > 0.05), and the area under the ROC curve was 0.888 (95%CI : 0.878-0.898). The average absolute error of Bootstrap repeated sampling 1000 times was 0.021, and the model C-index was 0.889 (95%CI: 0.888-0.991). The predicted probability of the model has a good consistency with the actual probability, with good accuracy, and the Brier score is 0.035 (95%CI: 0.015-0.054). Good clinical benefits can be achieved when the threshold probability is between 0.01 and 0.99. Conclusion The Nomogram model of PB in children with SMPP constructed based on factors such as fever duration, PIV, SII, D-D, LDH, and pleural effusion has good discrimination and accuracy, and can provide a reference for the prevention of PB.

OBJECTIVES: To investigate the regulatory effects of Aurora-A in regulating proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells and the role of actin-related protein 2/3 complex subunit 4 (ARPC4) in mediating its effects. METHODS: The plasmids pCDH-NC, pCDH-Aurora-A, and shRNA-ARPC4 were used for inducing Aurora-A overexpression or ARPC4 knockdown in HeLa cells. The cells were divided into vector group, Aurora-A overexpression group, Aurora-A overexpression+ARPC4 knockdown group, and Aurora-A overexpression+NF‑κBp65 inhibitor group and transfected with the corresponding plasmids. The proliferation, colony-forming ability, migration and invasion of the treated Hela cells was evaluated using EdU immunofluorescence assay, crystal violet staining, scratch assay, Transwell assay, and Matrigel assay. Western blotting was performed to detect the changes in cellular expressions of EMT-related proteins and expression levels of NF-κBp65 and ARPC4. RESULTS: The expression of ARPC4 was significantly decreased in HeLa cells with Aurora-A knockdown and increased in Aurora-A-overexpressing cells. Aurora-A overexpression obviously promoted proliferation, migration, and invasion abilities of HeLa cells, and these effects was significantly antagonized by ARPC4 knockdown. In Aurora-A-overexpressing cells, the phosphorylation level of NF-κBp65 and the expression level of ARPC4 were increased significantly, and application of the NF‑κBp65 inhibitor obviously lowered the expression level of ARPC4. CONCLUSIONS Aurora-A overexpression upregulates the expression of ARPC4 by activating the NF-κBp65 signaling pathway, thereby promoting migration, invasion and EMT of HeLa cells.
Humans ; Uterine Cervical Neoplasms/metabolism* ; Female ; HeLa Cells ; Epithelial-Mesenchymal Transition ; Signal Transduction ; Cell Movement ; Neoplasm Invasiveness ; Cell Proliferation ; Aurora Kinase A/metabolism* ; Transcription Factor RelA/metabolism* ; Neoplasm Metastasis

OBJECTIVES: To explore the molecular mechanism by which lncRNA SNHG15 regulates proliferation, invasion and migration of lung adenocarcinoma cells. METHODS: The lncRNA microarray chip dataset GSE196584 and LncBase were used to predict the lncRNAs that interact with miR-30b-3p, and their association with patient prognosis were investigated using online databases, after which lncRNA nucleolar RNA host gene 15 (SNHG15) was selected for further analysis. The subcellular localization of lncRNA SNHG15 and its expression levels in normal human lung epithelial cells and lung adenocarcinoma cell lines were detected using fluorescence in situ hybridization and qRT-PCR. In cultured A549 cells, the changes in cell proliferation, migration, and invasion following transfection with a SNHG15 knockdown plasmid (sh-SNHG15), a miR-30b-3p inhibitor, or their co-transfection were assessed with EdU, wound healing, and Transwell assays. Bioinformatics analyses were used to predict the regulatory relationship between lncRNA SNHG15 and COX6B1, and the results were verified using Western blotting and rescue experiments in A549 cells transfected with sh-SNHG15, a COX6B1-overexpressing plasmid, or both. RESULTS: LncRNA SNHG15 was shown to target miR-30b-3p, and the former was highly expressed in lung adenocarcinoma, and associated with a poor patient prognosis. LncRNA SNHG15 was localized in the cytoplasm and expressed at higher levels in A549 and NCI-H1299 cells than in BEAS-2B cells. In A549 cells, lncRNA SNHG15 knockdown significantly inhibited cell migration, invasion and proliferation, and these changes were reversed by miR-30b-3p inhibitor. A regulatory relationship was found between lncRNA SNHG15 and COX6B1, and their expression levels were positively correlated (r=0.128, P=0.003). MiR-30b-3p knockdown obviously decreased COX6B1 expression in A549 cells, and COX6B1 overexpression rescued the cells from the inhibitory effects of lncRNA-SNHG15 knockdown. CONCLUSIONS LncRNA SNHG15 may compete with COX6B1 to bind miR-30b-3p through a ceRNA mechanism to affect proliferation, migration, and invasion of lung adenocarcinoma cells.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/genetics* ; Cell Proliferation ; Cell Movement ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung ; Neoplasm Invasiveness ; A549 Cells ; Adenocarcinoma/genetics* ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor